Einstein Comprehensive Human Pluripotent Stem Cell Center

Eric Bouhassira, Ph.D.
Albert Einstein College Of Medicine

We propose here the creation of the Einstein Comprehensive Human Pluripotent Stem Cell Center that will help stem cell investigators make maximal use of their funds. The Center will be made of three units: a unit that will grow cells for investigators; a unit that will help investigators characterize their cells with modern techniques that create large amounts of data; and a unit to introduce human cells into mice to determine their properties in an animal model rather than in a dish. The proposed Center will maximize the use of all available stem cell research funds in Einstein through subsidized shared facilities. The facilities will perform procedures that are necessary to study stem cells but that are either repetitive, and therefore best performed by a core facility, or technically challenging and difficult to master except in specialized labs. The Center will also broadly disseminate stem cell technologies to the Einstein Community by providing training to members of the Community in the techniques available in the Center, by organizing stem cell seminars and journal clubs, and by offering pilot grants to facilitate initial experimentation by non-stem cell investigators.

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Confocal Microscope - Shared Equipment Grant

David Spector, Ph.D.
Cold Spring Harbor Laboratory (CSHL)

Investigators in three research groups at CSHL are conducting research on three distinct stem cell projects, all of which will provide valuable information that will enable the development of therapies for neurological diseases and cancer, as well as address fundamental mechanisms of gene regulation. An essential component of each of these projects is visualization of cells and tissues using a confocal microscope with multiple laser lines. These studies cannot currently be performed efficiently at Cold Spring Harbor Laboratory due to limited time availability on the existing confocal microscope as well as a lack of appropriate capabilities of the current instrument, which was purchased over 10 years ago. Specifically, the confocal microscope, funds for which are requested in this application, will allow CSHL scientists to visualize stem cells labeled with fluorescent dyes in order to estimate the number of stem cells, to observe the movement of stem cells and to observe differentiation of stem cells into specialized cells in living organisms.

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Cornell Mammalian Cell Reprogramming Core

John Schimenti, Ph.D.
Cornell Unversity

We propose to establish a core facility that will provide researchers at Cornell and in New York State access to cutting-edge technology and requisite expertise. The cornerstone of the facility will be an Induced Pluripotent Stem (iPS) Cell Core Laboratory, which will have the capability to derive embryonic-like stem cells from a variety of mammalian species including laboratory rodents. Uniquely, the core will also derive iPS cells from dogs, enabling translational research on the integration and effectiveness of cell-based therapies. The dog also presents unique opportunities to study the genetic basis of "stemness", as the genome exhibits less between-individual variation than humans, despite the enormous diversity in disease susceptibility and physical traits. This laboratory will have dedicated staff who will: 1) develop and quality-control the material for stem cell work, 2) derive, grow, and cryopreserve iPS cells from diverse species studied by interested scientists, and 3) train students and scientists to use the cells for various applications. This will make stem cell reprogramming technology available to a wide community of scientists that would otherwise not have the expertise or resources. The Core will be equipped for modern, high-throughput genomic analysis of iPS cells to help fully understand how reprogramming occurs and how experimental conditions can be optimized for controlling the cells in desired ways. The most important component will be a "next generation" DNA sequencer dedicated to the demands of stem cell research at Cornell. Importantly, a full-time bioinformatician will be hired to help scientists interpret the vast amounts of data generated by these analyses.

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The Sloan-Kettering Institute Stem Cell Research Facility

Lorenz Studer, M.D.
Memorial Sloan-Kettering Cancer Center

The Sloan-Kettering Institute (SKI) has been at the forefront of developing human embryonic stem cell (hESC) technologies. Thanks in part to the unique expertise at SKI, a stem cell facility was established in 2006. While several facilities for hESC research have been established in New York State, many of these facilities focus on trying to generate new stem cell lines. In contrast, our SKI stem cell research facility was designed to serve a complementary need. The main goal of the facility was to provide resources, expertise, and training in cutting-edge hESC research to the Tri-Institutional (Tri-I) research community (SKI, Weill Cornell Medical College, and The Rockefeller University). We were highly successful in this mission and less than 18 months after establishing our facility, we developed a broad user base within the Tri-I community, and the facility has been critical for several key technological breakthroughs. We propose to enhance both the scope and the capacity of our current facility via support from NYSTEM to match the increased user demand from the New York State community. Our scope will be enhanced by establishing a section within the facility dedicated to BAC technology that allows us to monitor how stem cells generate specialized fates in real time, and high-throughput technology, with which we can use hESCs in a robotic system to test the effects of thousands of molecules on stem cell behavior. These new additions to the facility will offer a service that is currently not available anywhere else in the state and will offer great benefit to the research community, including extensive training courses. Both technologies have great promise for harnessing the potential of stem cells in cell therapy and in the development of novel drugs for a variety of disorders.

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Human Embryonic Stem Cell (hESC) Core at Mount Sinai School of Medicine

Ihor Lemischka, Ph.D.
Mount Sinai School of Medicine (MSSM)

Our immediate goal is to develop and diversify hESC technology. To achieve this aim, the MSSM hESC Shared Resource Facility (SRF), henceforth 'hESC SRF,' has a three-faceted growth strategy. 1) Continue and extend research and development. Under this objective, the hESC SRF will continue its research into improving methodologies to maintain and differentiate hESCs. This technology will be extended to derivation of patient-specific Induced Pluripotent Stem (iPS) cells, their maintenance and differentiation. The hESC SRF will also facilitate the development of reagents important for stem cell research such as gene-targeted hESC lines and the generation of novel antibodies. These technologies will act in concert to improve the differentiation efficiencies of unmodified hESCs and iPS cell lines. 2) Quality control and supply. The hESC SRF will karyotype both hESCs and iPS cell lines as well as supply previously standardized reagents, cell lines and differentiated lineages to the scientific community. This service will have a two-fold benefit. Firstly, it will alleviate the quality control burden of individual scientists and allow them to concentrate on important scientific questions. Secondly, this service will allow collaborative projects involving hESCs to be initiated with non-ESC laboratories by removing the prohibitive cost and providing the expertise required to establish and sustain this technology. 3) Extend hESC technology by education and sharing of resources through instruction and collaboration, respectively. To enhance stem cell research in New York State and attract non-MSSM users, the hESC SRF has allied itself with similar facilities in New York City by contacting them directly and with institutions in New York State through its affiliation with the American Medical Schools of New York. In addition, the hESC SRF has established collaborations with the United Heath Network hESC Core Facility, Toronto, Canada, and with the hESC Core Facility at the Children's Hospital of Philadelphia.

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Shared Facility for Derivation, Distribution and Translational Research with Human Pluripotent Stem Cells

Scott Noggle, Ph.D.
The New York Stem Cell Foundation

The New York Stem Cell Foundation (NYSCF) established a highly successful stem cell derivation and characterization facility that will now be expanded to meet a growing need and to ensure that basic stem cell research and translational research to develop therapies advance in the same direction. The goal of NYSCF is to advance stem cell science that will result in cures for the major diseases of our time through excellence, collaboration and communication. To achieve this, we will expand our existing multi-institutional center to provide researchers with the following services and facilities: isolation of new embryonic stem cell (ESC) lines, creation of a stem cell bank for distribution of stem cell lines to researchers nationwide, training of junior and established researchers moving into stem cell research, derivation of disease and patient-specific cell lines using nduced pluripotent stem cell and somatic cell nuclear transfer technologies, comparison of human ESCs with stem cells derived by reprogramming approaches, developing improved/clinically approved methods for growing ESCs and directing them to specific cell types, preliminary design and screening for drug targets using stem cells, and research into normal ESC development to identify factors that lead to developmental abnormalities including cancers.

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NeuroBank

Sally Temple, Ph.D.
Regenerative Research Foundation

We propose to make our skills in neural stem cell (NSC) generation, characterization and cell culture available to other researchers via the development of a bank, designated 'NeuroBank,' for mouse and human NSCs, neural progenitor cells, induced pluripotent stem cells (iPSCs) derived from patients with neural diseases and neural lines derived from iPSCs (NiPSCs), collectively described hereafter as 'NSCs'. Each cell type offered would have an aligned database that will be online, searchable and live, so that researchers can add data and information as their work progresses. NeuroBank will be based in Albany, offering a centralized location for researchers throughout the state. Our first aim is to establish the NeuroBank infrastructure and website. The second aim is to begin line collection, including NSCs we create, and adding others through the four-year period that we and our users generate and request. Our third aim is to create 'made to order' engineered NSC lines for specific applications. Our fourth aim is to integrate the facility into the stem cell community by educating stem cell researchers about the benefits offered by the NeuroBank resource. This resource will greatly advance neural stem cell research in New York State, enabling experiments to produce the challenging variety of nervous system cells, and providing a consistent source of NSCs that can be used to develop models for drug screening or replacement therapies for neurological disease. New York has a strong position in NSC research and this facility will strengthen this to assure our future leadership.

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Shared Facilities and Resources for Stem Cell Research at The Rockefeller University and Weill Cornell Medical College

Ali Brivanlou, Ph.D.
The Rockefeller University/Weill Cornell Medical College

The Rockefeller University was the first academic institution in New York State to derive human embryonic stem cells using private funds, closely followed by the Ansary Center at Weill Cornell Medical College, and to date these remain the only institutions in the academic environment in New York State to have done so. Four tenured professors are involved in the effort to establish this shared facility. Each provides his/her own expertise and the expertise within their laboratories toward the successful accomplishment of the goals of this proposal in a synergistic manner. Establishing the facility will allow us to undertake a comparative study of human and mouse stem cells (embryonic and adult) and their relative abilities to differentiate into various specialized cell types. The derivation of novel human embryonic stem cell lines, reprogramming of somatic cells and differentiation into all three embryonic germ layers - ectoderm, mesoderm and endoderm - will allow us to develop specific cell-based therapy platforms and target specific diseases affecting: 1) the nervous system; 2) the skin; 3) the vasculature and blood; and 4) the liver and pancreas. These strategies should enable us to develop novel cell-based therapies and technologies that open novel avenues in modern medicine. By combining chemistry, genetics and cell biology of human embryonic stem cells, the group has all the expertise necessary and sufficient for the successful execution of the goals of the proposal. With the current investment of many states, especially in the field of stem cells in general, and in particular human embryonic stem cells not currently supported by federal funding, it is imperative for New York State to not fall behind the national and international efforts already underway to develop a resolution of these problems, which will have a tremendous impact in the clinic.

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Expansion of Humanized SCID Mouse Center & Stem Cell Processing Lab

Gerold Feuer, Ph.D.
SUNY Upstate Medical University

SUNY Upstate Medical University is unique among universities throughout the United States in having a center dedicated to "Humanized" SCID Mouse (SCID-HU mouse) research. SCID mice are immune deficient mice that develop a human immune system after injection with human hematopoietic stem cells. The SCID-HU model has the potential to become a broad platform for investigations of normal human stem cell and cancer stem cell biology, as well as human embryonic stem cell development. In addition, SCID-HU mice provide a powerful system for investigations on human pathogens such as HIV-1, dengue virus and malaria, and the testing of novel therapeutics against these pathogens. The Humanized SCID Mouse Center recently experienced a heightened interest, including multiple collaborations with investigators from New York State and institutions in other states. Funding from NYSTEM enabled purchase of an IVIS-200 whole-mouse imaging system in 2008 and increased the Center's visibility, researcher interest and usage. Notably, this novel imaging system will be used to track the engraftment and maturation of human stem cells in SCID-HU mice. The exciting advances in in vivo imaging that can be applied to stem cell research have the capacity to move the field rapidly forward. We also developed a Stem Cell Processing Lab so that isolation, expansion and analysis of stem cells in vivo can all be combined in one barrier facility. The existing Humanized SCID Mouse Center and the addition of the IVIS 200 imager represent a unique nexus of expertise that will facilitate and extend the goals of the Empire State Stem Cell Board by greatly accelerating research in stem cell development using in vivo models. Funds in the current application are now requested to expand and enhance the capacity of the existing Humanized SCID Mouse Center and Stem Cell Processing Laboratory and to test new SCID-HU models.

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